Background The aim of this systematic review is to determine microRNAs (miRs) that are differently expressed between diseased pulpal and periapical tissues. Design This systematic review used PubMed, Scopus, EBSCO, ProQuest, Cochrane database as well as manual searching to extract studies from January 2012 up to February 2022. Results A total of 12 studies met the eligibility criteria were included. All selected studies were of case-control type. Twenty-four miRNAs associated with apical periodontitis, 11 were found to be upregulatedand 13 were downregulated. Four out of the 44 miRs associated with pulpal inflammation were upregulated, whereas forty were downregulated. Six miRs, namely hsa-miR-181b, hsa-miR-181c,hsa-miR-455-3p,hsa-miR-128-3p, hsa-miR199a-5p, and hsa-miR-95, exhibited considerable downregulation in both periapical and pulp tissues. Conclusion MiRs have been investigated for their role in pulpal and periapical biology and may be utilised in diagnostic and therapeutic purposes. Further investigations are required to determine why certain irreversible pulpitis situations progress to apical periodontitis and others do not, based on the various miR expressions. Moreover, clinical and laboratory trials are needed to support this theory.